Vibrio Cholerae Clinical Trial
Official title:
An Open Label Post Licensure Trial to Evaluate the Safety and Immunogenicity of Indigenously Manufactured Killed Bivalent (O1 and O139) Whole Cell Oral Cholera Vaccine(Shanchol™)
The purpose of this study is to determine whether the killed bivalent (O1 and O139)whole cell oral cholera vaccine(Shanchol™) is safe and effective in the treatment of Vibrio cholerae.
Provision of safe water and food, establishment of adequate sanitation, and implementation
of personal and community hygiene constitute the main public health interventions against
cholera. These measures cannot be implemented fully in the near future in most
cholera-endemic areas. Improvements to water and sanitation require substantial long-term
investments, commitment from the local government, and often take years to implement. In the
meantime, a safe, effective and affordable vaccine would be a useful tool for cholera
prevention and control.
Considerable progress has been made during the last decade in the development of new
generation oral vaccines against cholera. These have already been licensed in some countries
and are now being considered for wider public health application. Cholera immunization is
now recommended for travelers to high risk areas, refugee camps and for outbreak response.
Furthermore, expanded use of cholera vaccines may be recommended for endemic areas, where
there is increasing demand from both low- and middle-income populations.
Starting in the mid-1980s, following technology transfer from Prof Jan Holmgren, Vietnamese
scientists at the National Institute of Hygiene and Epidemiology (NIHE) in Hanoi developed
and produced an oral, killed cholera vaccine for the country's public health programs. A
two-dose regimen of a first generation monovalent (anti-O1) cholera vaccine produced at US$
0.10 per dose underwent a field trial in Hue, Vietnam. The study was not formally
randomized: the vaccine was assigned on the basis of a systematic allocation scheme and the
control group did not receive a placebo. The calculated efficacy against El Tor cholera was
66% in fully immunized adults and children. Protection against non-cholera was assessed and
none was found suggesting a non-biased study design. Subsequently, killed 0139 whole cells
were added to the Vietnamese vaccine due to the emergence of the new form of epidemic
cholera caused by this serogroup. A study found the bivalent vaccine to be safe and
immunogenic in adults and children one year and older.
The Vietnamese vaccine has several distinct advantages over the Swedish vaccine. The
Vietnamese vaccine confers protection against the El Tor biotype in younger children. And
the price of US $0.10 per dose is feasible for public health programs in developing
countries, while the Swedish vaccine is prohibitively expensive. Finally, it can be
administered without a buffer, while the Swedish vaccine requires a buffer and stricter cold
chain requirements.
Since licensure of the oral cholera vaccine in Vietnam, more than 9 million doses have been
administered without any report of serious adverse events. The vaccine is produced according
to recommended guidelines at the Company for Vaccine and Biological Production No. 1
(VABIOTECH) in Hanoi. VABIOTECH is working towards WHO Good Manufacturing Practices (GMP)
certification, which they hope to receive in the next few years. At the same time, the IVI
and VABIOTECH have been working to internationalize the Vietnamese vaccine for global use.
In order to comply with WHO requirements, the vaccine was reformulated.
Phase II trials of this reformulated killed oral cholera vaccine were performed in SonLa,
Vietnam and Kolkata, India where the vaccine was found to be safe and no serious adverse
reaction was associated with the vaccine. The vaccine elicited significant vibriocidal
antibody responses among vaccinees. In SonLa, 90% of adult recipients seroconverted to V.
cholerae O1 following receipt of two doses of the vaccine. In Kolkata, 53% of adults and 80%
of children aged 1-17 years developed 4-fold and greater rises in vibriocidal antibodies to
V. cholerae O1. Data from Vietnam and India suggest that greater magnitudes in the
vibriocidal responses following 2 doses of the vaccine are elicited compared to previous
formulations. It has been suggested that this response may correlate with the higher
lipopolysaccharide content of the vaccine, a result of changes in its standardization.
A phase III trial of this vaccine is currently underway in Wards 29, 30, and 33 of Kolkata,
India. Since this trial is still ongoing, data regarding adverse events still has not been
analyzed. As yet no serious adverse reaction has been directly attributed to the vaccine.
Surveillance continues in these areas to determine the efficacy of the vaccine.
Through an agreement negotiated by the IVI, VABIOTECH produced the bulk reformulated
bivalent vaccine under quality conditions supervised by the IVI. Shantha Biotechnics of
India filled and finished the bulk, and obtained regulatory clearance for use of the vaccine
in Phase II and III trials in India. In return, the technology for future production of the
oral killed bivalent cholera vaccine was transferred to Shantha Biotechnics.
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Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT01524640 -
Bridging Study for Killed Oral Cholera Vaccine in Ethiopia
|
Phase 4 |